Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical tretinoin therapy produces clinical improvements in the fine wrinkling of photodamaged skin, possibly by enhancement of collagen synthesis. A major biochemically and histologically detectable change in photodamaged skin is the accumulation of abnormal elastic fibers (elastotic material). However, little is known about the effects of retinoic acid and ultraviolet B (UVB) on elastin gene expression. Consequently, we examined the effects of all-trans-retinoic acid (t-RA) and UVB on elastin gene expression in cultured human skin fibroblasts in vitro. Elastin mRNA gene expression was up-regulated in response to UVB by approximately equal to 3-fold, in a dose dependent manner, between 3 and 10 mJ/cm2 doses. Similar results were obtained by chloramphenicol acetyltransferase assay, in which a maximal promoter activation more than 5.4-fold that in nonirradiated controls occurred after a single dose of 20 mJ/cm2. Also t-RA inhibited the increase in elastin mRNA level following a single exposure to UVB by approximately 16%, and the increase in promotor activity by about 65%. The inhibitory effect of t-RA on elastin induced by UVB was also demonstrated by indirect immunofluorescence studies. Taken together, t-RA down-regulated human elastin gene expression elevated by a single exposure to UVB at transcriptional and possibly protein levels. These results suggest that the anti-photoaging effect of t-RA may be related, at least in part, to down-regulation of elastin gene expression elevated by UVB.
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PMID:All-trans-retinoic acid down-regulates elastin promoter activity elevated by ultraviolet B irradiation in cultured skin fibroblasts. 969 46

We have previously shown in a transgenic mouse line, in which 5.2 kb of the elastin promoter was linked to the reporter enzyme chloramphenicol acetyltransferase (CAT), that the highest levels of expression were found in embryonic lungs and aorta, while lower levels were detected in other elastin-containing tissues. Furthermore, in general, expression of the transgene showed developmental regulation similar to that of the endogenous gene. However, the precise location of cellular expression could not be determined in this model. To overcome this limitation, we have developed a similar model, but replaced CAT with the reporter enzyme beta-galactosidase. Enzyme activity was readily detected in the transgenic mouse embryos in expected regions of tissue forming elastic fibers, including the dermis and elastic cartilage. Of considerable interest, however, was the novel finding of expression in specific areas of neuroepithelium of the brain and in the perichondrium surrounding areas destined to form hyaline cartilage in endochondral bone formation. These latter areas included all the bones of the limbs, the spine and rib cage. It appeared that these segments of elastin expression demarcated the border between the developing cartilage and the surrounding mesenchymal tissue. Elastin promoter expression was also found in developing somites, in the mesenchymal layer of the forming cornea of the eye, in the genital tubercle and in the epithelium destined to form the olfactory epithelium. These findings indicate that the elastin promoter is activated during embryonic development in a variety of tissues, suggesting that elastin gene expression may play a role in organizing cutaneous, skeletal and neural structures.
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PMID:Expression of the elastin promoter in novel tissue sites in transgenic mouse embryos. 1076 40

Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elastase activity after BA in a rabbit arterial double-injury model and the effects of elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective inhibitors of serine elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan-liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chloramphenicol acetyltransferase-transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28+/-0.22 versus 0.16+/-0.07 mm(2) for CAT-transfected versus elafin-transfected arteries, respectively; P<0.05). These data suggest that an early increase in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.
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PMID:Arterial elastase activity after balloon angioplasty and effects of elafin, an elastase inhibitor. 1149 52